Category Archives: Live

Job: Postdoc position in proteome bioinformatics

I currently have an opening for a two-year postdoc position in my group Cellular Network Biology at the Novo Nordisk Foundation Center for Protein Research.

The project primarily relates to on computational analysis of mass-spectrometry-based proteomics data. This includes developing new, improved methods for analyzing spectra, optimization of analysis protocols, and application of these to specific datasets. The focus will be on improving the identification of post-translationally modified peptides, which arise in cellular signaling processes and through chemical modification, in particular in ancient samples, which may also consist of mixtures of species. The work will involve close collaboration with the Proteomics Program.

The closing date for applications is December 31, 2014. For further details refer to the job advert.

Advertisements

Live: Lecture by Nobel Laurate Avram Hershko

Today I am at the the symposium “Protein Chemistry ‐ Applications to Combat Diseases”, which takes place in Copenhagen a few minutes walk from where I work.

This morning started with a keynote lecture by Nobel Laurate Avram Hershko on regulation of the cell division cycle by ubiquitin‐mediated protein degradation. This post is just a very quick write-up and a few photos made during and immediately after his presentation.

Avram Hershko presenting in Copenhagen

Most of the early work on ubiquitylation was done on model proteins, most of which were extracellular. Interestingly, what spurred Avram Hershko on to study ubiquitylation of physiologically relevant proteins was the early work on cyclin degradation for which Tim Hunt received the Nobel Prize. Tim Hunt speculated speculated that there was a cyclin protease that would break down cyclins. However, Avram Hershko showed in 1991 that cyclins are in fact not degraded by a specific protease, but are rather targeted for proteasomal degradation by a specific ubiquitin ligase. Showed this in JBC papers in 1991 and 1994. One year later his group identified this ubiquitin ligase to be what is now known as the Anaphase Promoting Complex (APC) / Cyclosome (APC/C).

The role of APC/C in ubiquitylation and degradation of cyclins

In addition to being crucial for degradation of cyclins, APC/C is also required for entry into anaphase of the cell cycle (hence the name Anaphase Promoting Complex). This because it is responsible for targeting the securin protein for degradation, which in turns releases separase activity to degrade the cohesin rings that hold together sister chromatids.

Having worked on other cell-cycle proteins for many years, Avram Hershko has in recent years returned his interest to APC/C, more specifically to understand how the inhibition of APC/C is released, which in turn leads to the whole series of events described above.

Release of APC/C from checkpoint inhibition

Live: Bioinformatics for Molecular Biologists

I have now arrived in Bertinoro where I will be lecturing on the 8th Course in Bioinformatics for Molecular Biologists. And after a fight with network configuration and power outages, I also eventually managed to get online.

All the speakers are housed at the castle, which has a fantastic view over the surrounding area – also by night:

Night view from the castle

The scientific part of the meeting was kicked off by H. Werner Mewes:

Opening lecture by H. Werner Mewes

I am sure there will be many interesting lectures to follow – and I hope that the audience will think that mine is one of them.

Live: Evolution of biological pathways

Orkun Soyer has just finished his excellent presentation at CoSBi on the use of toy models for understanding the principles that govern biological pathways, in particular signaling pathways. One can obviously imagine several scenarios for how pathways came about:

Evolution vs. intelligent design

The key point, however, is that we might be able to understand something about pathways through computational studies of simple toy models. The toy model discussed throughout the talk was bacterial chemotaxis:

Evolving “chemotaxis” in a computer

The idea is that evolution can to some extend be approximated as an optimization process, in which the objective function corresponds to fitness. In case of the “tumble or swim” problem, computational simulations allowed simple regulatory network to evolve that mimic the food-finding behavior of bacteria.

He also presented an interesting view on how biological complexity has evolved. The idea is to show how complex systems can evolve even if assuming a (weak) selection against complexity:

Modeling the evolution of complexity

I think that his results provide a lot of insight into how real signaling may have evolved, although all the simulations are based on simplistic toy models. I recommend that you download Orkun Soyer’s slides if you want to know more.

This talk ends the Computational and Systems Biology course at CoSBi.

Live: Networks, noise and survival in stress

Gabor Balazsi has just finished a very interesting presentation on the interplay between molecular networks, gene expression noise, and evolutionary selection – here is the opening slide:

Garbor Balazsi’s opening slide

In the first part of his talk he gave a nice introduction to global network topology and network motifs – this should be nothing new to people familiar with the work of the Barabasi and Alon labs. He also explained the “Commander, Intermediate, Executor” model for hierarchical regulatory networks, which I had personally not heard about before, and the concept of “origons”, which seems quite use for understanding the response of large signaling networks to environmental cues.

The second part of his talk was about stochastic noise in gene expression. Genetically identical cells in a culture may express the same protein at different levels; this is a result of random noise influencing transcription, mRNA degradation, translation, and protein degradation. This is simply a consequence of low copy numbers giving rise to stochastic, as opposed to deterministic, behavior.

Finally, he talked about how noise at the level of gene expression can influence the survival of species in a changing environment. This part of his talk was kicked off with the funniest slide of his presentation:

Gabor Balazsi’s funniest slide

I guess it should be seen as a lesson on how not to do. He made some very good points about how noise plays hardly any role in multicellular organisms that reproduce sexually. By contrast, stochastic variation within clonal bacterial cultures provides much higher chance of survival when faced with sudden stress such treatment with anti-bacterial drugs. I would have liked to hear more about this, but unfortunately there was not much time left for this part of the presentation due to technical problems with the projectors. It looks like Guy Shinar picked the safe strategy for his presentation.

All in all, I found it to be a really inspiring talk. I have uploaded his slides in case if you want to take a look at it.